Subsets of Patients with Aplastic Anemia Identified by Flow Microfluorometry

Anti-thymocyte globulin (ATG) provides effective therapy for many patients with aplastic anemia, and its mechanism of action has been presumed to be secondary to lymphocytotoxicity. However, our studies of lymphocyte function in aplastic anemia show marked abnormalities of lymphokine production, which ATG may modulate. In 12 of 17 patients with aplastic anemia, interleukin 2 (IL2) production was markedly elevated in vitro (P less than .01 by paired statistical analysis). Expression of the IL2 receptor, or Tac antigen, on peripheral lymphocytes assessed by flow microfluorometry was also increased above the normal range in 11 of 15 cases. Studies of ATG suggested that it might act to stimulate lymphocyte function. In vitro, ATG is a mitogen, as measured by incorporation of 3H-thymidine into blood mononuclear cells; the response of cells to ATG from patients with aplastic anemia was exaggerated in comparison with normals. Cell proliferation was accompanied by production of IL2 to levels that were, in some cases, similar to those obtained with lectin stimulation. Finally, supernatants from lymphocytes cultured in the presence of ATG were able to replace adherent cells in providing growth factors for the support of nonadherent cells in methylcellulose hematopoietic colony assays. These results provide a mechanism for an “immunostimulatory” action of ATG in effecting hematopoietic response in some patients with aplastic anemia.

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Lymphokine abnormalities in aplastic anemia: implications for the mechanism of action of antithymocyte globulin

Blood ◽

10.1182/blood.v65.2.407.407 ◽

1985 ◽

Vol 65 (2) ◽

pp. 407-413 ◽

Cited By ~ 84

Author(s):

P Gascon ◽

NC Zoumbos ◽

G Scala ◽

JY Djeu ◽

JG Moore ◽

...

Keyword(s):

Aplastic Anemia ◽

Mechanism Of Action ◽

Mononuclear Cells ◽

Interleukin 2 ◽

Lymphocyte Function ◽

Normal Range ◽

Flow Microfluorometry ◽

Nonadherent Cells ◽

Hematopoietic Response

Abstract Anti-thymocyte globulin (ATG) provides effective therapy for many patients with aplastic anemia, and its mechanism of action has been presumed to be secondary to lymphocytotoxicity. However, our studies of lymphocyte function in aplastic anemia show marked abnormalities of lymphokine production, which ATG may modulate. In 12 of 17 patients with aplastic anemia, interleukin 2 (IL2) production was markedly elevated in vitro (P less than .01 by paired statistical analysis). Expression of the IL2 receptor, or Tac antigen, on peripheral lymphocytes assessed by flow microfluorometry was also increased above the normal range in 11 of 15 cases. Studies of ATG suggested that it might act to stimulate lymphocyte function. In vitro, ATG is a mitogen, as measured by incorporation of 3H-thymidine into blood mononuclear cells; the response of cells to ATG from patients with aplastic anemia was exaggerated in comparison with normals. Cell proliferation was accompanied by production of IL2 to levels that were, in some cases, similar to those obtained with lectin stimulation. Finally, supernatants from lymphocytes cultured in the presence of ATG were able to replace adherent cells in providing growth factors for the support of nonadherent cells in methylcellulose hematopoietic colony assays. These results provide a mechanism for an “immunostimulatory” action of ATG in effecting hematopoietic response in some patients with aplastic anemia.

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Maytansine-Induced Mitotic Arrest in Human Lymphoblasts

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079747 ◽

1977 ◽

Vol 35 ◽

pp. 460-461

Author(s):

Tai-Te Chao ◽

John Sullivan ◽

Awtar Krishan

Keyword(s):

Electron Microscopy ◽

Cell Cycle ◽

Transmission Electron Microscopy ◽

Tubulin Polymerization ◽

Vinca Alkaloids ◽

Antimitotic Activity ◽

Transmission Electron ◽

Flow Microfluorometry ◽

Brain Tubulin

Maytansine, a novel ansa macrolide (1), has potent anti-tumor and antimitotic activity (2, 3). It blocks cell cycle traverse in mitosis with resultant accumulation of metaphase cells (4). Inhibition of brain tubulin polymerization in vitro by maytansine has also been reported (3). The C-mitotic effect of this drug is similar to that of the well known Vinca- alkaloids, vinblastine and vincristine. This study was carried out to examine the effects of maytansine on the cell cycle traverse and the fine struc- I ture of human lymphoblasts.Log-phase cultures of CCRF-CEM human lymphoblasts were exposed to maytansine concentrations from 10-6 M to 10-10 M for 18 hrs. Aliquots of cells were removed for cell cycle analysis by flow microfluorometry (FMF) (5) and also processed for transmission electron microscopy (TEM). FMF analysis of cells treated with 10-8 M maytansine showed a reduction in the number of G1 cells and a corresponding build-up of cells with G2/M DNA content.

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Aplastic anemia associated with submassive hepatic necrosis. Report of four cases

Archives of Internal Medicine ◽

10.1001/archinte.137.7.898 ◽

1977 ◽

Vol 137 (7) ◽

pp. 898-901 ◽

Cited By ~ 1

Author(s):

P. Watananukul

Keyword(s):

Aplastic Anemia ◽

Hepatic Necrosis

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Homeopathy in a child with “very severe aplastic anemia”

Allgemeine Homöopathische Zeitung ◽

10.1055/s-0037-1601204 ◽

2017 ◽

Vol 262 (02) ◽

pp. 2-76

Author(s):

C Schuldt

Keyword(s):

Aplastic Anemia ◽

Severe Aplastic Anemia

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TO STUDY THE ETIOPATHOLOGICAL SPECTRUM OF ADULT PATIENTS WITH PANCYTOPENIA

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v4i10.1461 ◽

2020 ◽

Vol 4 (10) ◽

Author(s):

Harimohan Garg ◽

Haritej Anand Khirawari ◽

Sona Priyadarshi

Keyword(s):

Acute Leukemia ◽

Aplastic Anemia ◽

Indian Subcontinent ◽

Megaloblastic Anemia ◽

Anaplastic Carcinoma ◽

Adult Patients ◽

Research Centre ◽

New Delhi ◽

Nutritional Anemia ◽

Male Preponderance

Background: Pancytopenia is diagnosed when there is a reduction in all three hematopoietic cell lines. Till date there is limited number of studies on the frequency of various causes of pancytopenia. Of these some have been reported from the Indian subcontinent. There appears to be a changing spectrum of pancytopenia over the past two decades. The objective was to study the etiopathological spectrum of adult patients with pancytopenia over a period of one and half year. Methods: The Prospective and retrospective observational study was conducted in the Department of Family Medicine, Batra Hospital and Medical Research Centre, New Delhi. A total of 120 Patients were included in the study. All patients gave their consent to take part in the study and were subjected to a questionnaire regarding symptoms, past relevant history, lifestyle and detailed clinical examination and investigations as mentioned in materials and methods. Results: Six broad diagnostic groups could be identified in adults with pancytopenia. Megaloblastic anemia (D1) was the largest group comprising 57.5% of all patients. 11.7% of patients with pancytopenia were diagnosed as Aplastic anemia (D2).11.7% of patients with pancytopenia were diagnosed as leukemia/lymphoma (D3) such as lymphoma (1), metastatic anaplastic carcinoma (1), acute leukemia (11), and metastatic gastric carcinoma (1). 15% of patients with pancytopenia were diagnosed with infections (D4) such as complicated malaria cases (7), HIV (5), disseminated tuberculosis (4), viral (2). We also encountered (D5) 0.8% was Myelophthisis/Storage disorder as myelodysplastic syndrome (1) and 3.3% were other (D6) as reactive marrow (4). Conclusion: Pancytopenia is not a disease itself. It is a hematological feature of varying etiology with slight male preponderance. Megaloblastic anemia along with mixed nutritional anemia is leading cause of pancytopenia in India followed by infections being second and aplastic anemia and acute leukemia being third common causes. Keyword: Pancytopenia, Megaloblastic anemia, Nutritional anemia.

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